Transverse myelitis: a question and an answer

A question from one of my readers. My reply to it follows.

 

 

Dear Sir/Madam,

I am under a Neurologist’s care at present. A few weeks back I had tingling, numbness, stiffness in my right wrist, within days/hours this spread from my hand to my neck all the way down the right side of my body. CAT scan and xray clear. MRI scan shows an abnormality within the upper part of the cervical spine consistent with demyelination. Also shows a single small focus of abnormal signal in the left frontal region. He feels it possible I may have an isolated episode of tranverse myelitis. I also have an odd sensation when I put my chin on my chest, I have felt this for approx 6 months plus, it feels like an elastic band stretching, not painful just an odd feeling. The symptoms have not got better 3 weeks on and now I feel the same tingling in my left fingers the same as this started in the right side. I have been given MEDRONE today (19/12/11) 100mg and told to take 5 tablets all in one go so I have 500mg dose. Not sure I like the feeling that comes with these tablets and thats spacing them out, don’t think I could take them all together. Any feed back would be greatfully appreciated. I’m 41 years old, fit and healthy usually, work hard, mum of 2. Just had an early diagnosis of menopause. Many thanks. Kind regards. N

 

 

Dear N,
thank you for writing in to me. From your history it seems you were diagnosed with transverse myelitis. Transverse myelitis (TM) as the name suggests is an inflammatory process of the spinal cord and usually involves the cervical or thoracic spinal cord. MRI of the cervical spine further helps to characterize it: complete TM Vs incomplete TM.

 

There can be many causes of TM: inflammatory/demyelinating (multiple sclerosis among other diseases), infectious causes, paraneoplastic, postvaccinal (drugs and other toxic causes) and autoimmune/collagen vascular diseases. Sometimes inspite of an extensive work-up no cause can be determined. This is termed idiopathic TM.

 
Based on the site and extent of the lesion, the symptoms vary. If the patient has a complete TM high up in the cervical cord (like around C5-C6): there is usually involvement of both arms and legs (quadriparesis). The bladder and bowel function may also be affected. If the lesion is small and eccentrically placed in the cervical cord (incomplete TM), the symptoms may not be so symmetrical and the patient may present with numbness and weakness in one arm and leg. If the lesion is below C6-C7, usually the arms are spared and only the legs are involved.

 
You say you experience an odd sensation when you put your chin to your chest. What you are experiencing is called the Lhermitte’s sign (LS). It is an electric/shock like sensation which runs down the back and into the limbs and is elicited by bending the head forward. This occurs because the nerve tracts (dorsal columns which carry sensations such as joint sense, vibration sense and position sense) running down the cervical spine are damaged. LS is a nonspecific sign and can be seen in many diseases which involve the dorsal columns. Transverse myelitis is one such disease process and hence this sign can be elicited in some patients.

 
Once a patient is diagnosed with TM, an extensive evaluation is carried out to determine the cause of TM. The diseases some of which I have mentioned before are looked for and meticulously excluded. MRI of the brain and other tests to rule out multiple sclerosis may be carried out (as it seems were done in your case) to secure the diagnosis–is the TM because of some underlying disease and if so what is the disease or is the TM truly idiopathic?

 
Treatment of TM depends upon the cause of TM. Like for example if the TM is due to a demyelinating disease such as multiple sclerosis, the treatment involves treatment of MS with immunomodulating drugs. If the cause is infectious, then the underlying infection is treated. If the patient has idiopathic TM and in some cases of inflammatory MS, then based on the time of your clinical presentation, your doctor may decide to treat you with high dose steroids (usually 500-1000mg of methylprednisolone is given once a day for 3 to 5 days). This helps to hasten recovery.

 
I hope I have answered some of your questions N.

Personal Regards,

Nitin Sethi, MD

 

A question about oligoclonal bands (OCBs) in multiple sclerosis and a reply

Recently one of the readers of my blog asked me a question about the presence of oligoclonal bands (OCBs) in multiple sclerosis. I am reproducing her question here and my reply to is follows. Hope it helps some of you out there.

 

Hello Dr. Sethi:
I found your informative blog Brain Care Foundation online, and I wanted to get in touch with you about the neurological symptoms I have been experiencing in hopes that you can provide some guidance to me.

I am a 28-year-old Indian-American female who was recently diagnosed with optic neuritis. An MRI of my brain showed one unspecified speck and a lumbar puncture showed three oligoclonal bands that were also present in the blood, ruling out multiple sclerosis, according to my doctor. All other blood work is normal.

She has recommended that I see a rheumatologist to rule out other autoimmune diseases.

I have been very concerned about underlying diseases that may have causes the optic neuritis and my question to you is whether I should be concerned about the presence of three oligoclonal bands in the cerebral spinal fluid. Ideally, I understand there would be none, but it seems somewhat arbitrary to me that 1 or 2 would be considered normal and 3 would be considered an abnormally high level.

I specifically wanted to seek your advice because I read in your blog that “greater than 3” would be the amount of concern.

Thank you in advance for any insight you can provide.

Sincerely,
R

p.s. please feel free to post this question on your blog without using my name

Dear R,

thank you for writing in to me. You ask me a very specific question regarding the presence of OCBs in multiple sclerosis (MS) and I shall be happy to answer it for you. OCBs can be seen in multiple other conditions apart from MS. What we look for in MS is that the oligoclonal bands should be only present in the cerebrospinal fluid (CSF) and not in the blood. As you are aware MS is a demyelination disease of the central nervous system (brain and spinal cord). So it reasons that the bands should only be present in the spinal fluid and not in the blood. We refer to this as intrathecal synthesis of OCBs. If OCBs are present in both the spinal fluid and the blood, one needs to rule out diseases that may cause passive transfer of OCBs from the blood into the spinal fluid. Now to your second question. Just how many OCBs are considered abnormal or worrisome for MS? This is a tough one to answer as studies have shown conflicting results. Some studies have indicated that a higher number of OCBs in the spinal fluid is more specific for MS (aka increases the risk for conversion of a clinically isolated syndrome into a clincally definite MS). In other studies this has not been conclusively proven.

Hope that answers your queries. I wish you my ver best.

 

Personal Regards,

Nitin Sethi, MD

White matter lesions, migraine and memory problems: a question and an answer

One of the readers of my blog wrote in with a question about white matter lesions on brain MRI. Her question and my response to it follows.

Question:

I was recently referred to a neurologist by my primary care physician for treatment of my migraines. While migraines have a been a part of my life, they have been occuring with greater frequency of late (10+ per month). To rule out any other cause of my migraines, the doctor ordered an MRI. The MRI revealed 20+ white matter lesions throughout my brain (various locations, various sizes). The neuro was at a loss as to why I had so many. I did inform him that approx 15 years ago I had unilateral ect, and asked if perhaps this had caused it? I also let him know that I was experiencing significant memory issues (forgetting short term and long term memories, and even blanking on spelling my own last name for a minute or two). I asked him if ect could be responsible? The neuro has since followed up with me and has stated that ect could NOT be responsible for the lesions, and was not likely to be responsible for my recent, memory issues. I have been tested for MS, lyme, infection, etc. – all negative. I do not suffer from depression or take any other medications which would cause memory issues. Any thoughts? What else could cause these lesions? Is these any research at all into lesions and ect? I am trying to get into Neuropsych testing to determine the extent of my memory loss. The migraines are now currently being sufficiently controlled with Imitrex.

Answer

Thank you for writing in to me M.  White matter lesions are commonly documented on brain MRI done for various reasons (in your case as a work up of migraines). The differential diagnosis of white matter lesions is broad and varies based on the age of the patient. In “most” adult patients especially those with risk factors for microvascular disease such as diabetes mellitus, essential hypertension (high blood pressure), dyslipidemia (high cholesterol), current or past heavy smokers these white matter lesions respresent small vessel disease (also referred to as microvascular ischemic small vessel disease). Meaning that the small blood vessels in the brain are showing signs of ischemia (lack of blood flow). So when I see extensive microvascular (small vessel) disease on a patient’s MRI scan of the brain what I worry about is the possibility of a stroke in the future. As a neurologist, I then try to identify his stroke risk factors and attempt to modify them. If he has high blood pressure and is not an on anti-hypertensive medication–start an appropriate anti-hypertensive, if he is already taking a blood pressure medication but the blood pressure is still not well controlled then I may need to increase the dose of his medication and/or change it. As per the new Joint National Commission guidelines broadly speaking the lower the blood pressure the better it is (earlier a blood pressure of 140/80 mm Hg was accepted as ” normal”, now we aim for level of 120/70 mm Hg). If the patient’s blood sugar is high (fasting blood sugar greater than 107mg/dl), I would investigate him for diabetes mellitus. For this blood sugar is tested in a fasting state and after meal (post prandial). There are normal values and if the patient’s blood sugar exceeds these normal values, then he has diabetes mellitus. Diabetes mellitus can be controlled by a combination of dietary modification, exercise, oral hypoglycemic medications (pills) and/or insulin injections. If the lipid profile is deranged (high total cholesterol, high low density lipoprotein, high triglycerides and low high density lipoprotein), then again dietary modifications, exercise and lipid lowering medications (statin group of medications such as Lipitor are one example) are recommended.

Now what do white matter lesions represent when they are seen in a young person (like for example in a  young lady 25 years of age)?  The main differential and what concerns most patients and physicians alike is whether this could represent multiple sclerosis. I have written about this before and again want to emphasize that the diagnosis of multiple sclerosis is a clinical one and not based solely on the MRI scan of the brain. The MRI scan always has to be interpreted after taking the history and examination findings into consideration. Also the white matter lesions of ischemic small vessel disease are different from the white matter lesions (plaques) of multiple sclerosis. In multiple sclerosis the lesions have a characteristic appearance and distribution in the brain.

White matter lesions can also be seen in many other infectious (Lyme disease is a good example) and inflammatory conditions (sarcoidosis, connective tissue diseases which cause vasculitis in the brain). Most of these diseases can be identified with the help of a good history and some basic tests.

White matter lesions are also commonly seen in people who suffer from migraines (more commonly seen in women migraine sufferers). Why do white matter lesions occur in migraine patients. While there are many theories of migraine pathophysiology, migraine is a vascular headache and hence the blood vessels are again involved.

Do white matter lesions cause memory problems. Now that is a tough question to answer. When I see extensive white matter disease in a brain MRI, it tells me about the health of the brain and the blood vessels. If a person has extensive white matter disease, the same pathology shall be seen in the blood vessels of the heart. So they are prone to both heart disease and brain disease (stroke, transient ischemic attacks). While Alzhemier’s disease is the most common primary dementia, vascular dementia is exceedingly common too. What is vascular dementia? As the name suggests, it is dementia (memory impairment, problems in multiple cognitive domains) caused due to multiple small strokes in the brain or rather strokes in a strategic location. These strokes occur over a period of time and may be clinically silent (meaning that the patient may not even realise that he has suffered a stroke). The small strokes over a period of time though add up and cause vascular dementia.

I hope this helps in answering some of your questions M. My advise to you is to follow up with your primary care physician and the neurologist. They shall help guide your work-up further.

Personal Regards,

Nitin Sethi, MD

Not all tremors represent Parkinson’s disease

Patients frequently come to see me for evaluation of their tremor.  Invariably the history is that the tremor was first brought to their attention by a close friend or a family member. The patient is worried that he/she has Parkinson’s disease and hence seek a neurologist’ s attention. Rarely are they bothered by the tremor per-se. By that I mean the tremor is usually not disabling and does not impair their quality of life at least initially. So do all tremors represent Parkinson’s disease? Are there any benign tremors? Which tremors warrant medical attention? These are some of the issues I plan to dwell on in this blog post. I hope some of my readers shall find the information useful.

So what exactly is a tremor. Well neurologically a tremor is characterized by rhythmic oscillatory and involuntary movement across a joint. I used the work involuntary because tremors at times can be voluntary. Voluntary tremor is usually psychogenic (meaning it has a psychological basis to it). We shall not discuss psychogenic/voluntary tremors in this post though. Suffice to say that a doctor shall be able to identify psychogenic tremor based on the history and examination findings alone.

So what do I look for when a patient with tremor comes to me seeking an explanation. Well the age of the patient is the first clue to the etiology of the tremor. Idiopathic Parkinson’s disease usually starts off in the sixth to seventh decade of life. Familial Parkinson’s disease can start at a younger age but usually the tremor is not so prominent nor is it the initial manifestation. There can be many causes of tremor in the “young”.  Various medical conditions some more common such as hyperthyroidism, hepatic and renal diseases and some more exotic such as Wilson’s disease (due to a problem with copper metabolism in the body)come to mind.  At times the answer is more innocuous and the tremor is either due to stress or excessive intake of coffee and other caffeine containing drinks. In that case all that is needed is reassurance. One other disease that needs to be kept in mind is multiple sclerosis though usually more findings are documented in exam (meaning that the tremor is not see in isolation). One should never forget to ask patients about the use of prescription, over the counter and illicit drugs. Many drugs such as sodium valproate (commonly used to treat seizures and at times bipolar disorder), bronchodilators (drugs used to treat asthma, reactive airway disease and chronic obstructive airway disease) cause a coarse postural and kinetic tremor as a side-effect. Once the drug is stopped the tremor abates.

Another common entity frequently confused with Parkinson’s disease is what is called essential tremor or also sometimes referred to as benign essential tremor. Patients who have essential tremor are usually in the same age group as patients with idiopathic Parkinson’s disease and hence the confusion and concern arises. Essential tremor has the following characteristics: it is usually a postural tremor (meaning that the tremor is most prominent when the hands are kept out and maintained at a posture such as having them stretched out in front of you. Remember the classical tremor of Parkinson’s disease is a resting tremor. Meaning the tremor is most prominent when the hands are at rest like for example resting on the patient’s lap and the patient’s attention is diverted). Essential tremor is a faster and finer tremor as compared to the tremor of Parkinson’s disease which is a slower (2-5 Hz) and of higher amplitude. A point to note here is that tremors are frequently classified based on their frequency, amplitude and position (rest Vs postural Vs kinetic).  Patients who have essential tremor frequently in addition to the hand tremor also may have a head tremor (the head shakes either from side to side [no-no tremor] or up and down [yes-yes tremor]). They may also have a tremor in their speech (voice tremor). On further questioning some of them may admit to having the tremor run in their family (meaning their father and grandfather also had a similar tremor). They may have also noted that when they drink alcohol the tremor becomes less prominent.  Infact some patients start drinking excessively for this very reason! Essential tremor usually progresses very very slowly (if at all) and may never become problematic and disabling in the patient’s lifetime.  Hence it does not need to be treated unless it is socially disabling (“Doctor Sethi I cannot drink a glass of wine without spilling it over my dress!” “Dr Sethi  I am so embrassed when my hands shake in a business meeting!”). Essential tremor is not accompanied by the other signs and symptoms which accompany Parkinson’s disease such as gait problems, freezing, stiffness, rigidity and mask like facies.

So not all tremors represent Parkinson’s disease. A quick visit to your “local” neurologist shall give you an answer to what kind of tremor you have.

Multiple sclerosis: making the diagnosis

So let us start from where we left off. Just how do we (doctors) go about making (confirming) the diagnosis of MS.

MRI scan: Well one of the test most commonly requested (infact done in nearly every patient) is a MRI scan of the brain and at times of the cervical spinal cord. What are we looking for you may ask? Well multiple sclerosis on the MRI is characterized by plaques (lesions) which are disseminated in space and in time. What does that mean? In a typical patient of MS, the MRI scan shall show evidence of disease activity which is scattered around in different parts of the brain. Meaning there are MS lesions seen in different parts of the brain white matter (typically MS is a white matter disease though recent research indicates involvement of the grey matter too). So for example a typical MRI scan shall show plaques scattered  in the white matter of the frontal lobe, parietal, temporal lobe, cerebellum and so forth. Moreover the MRI scan shall indicate that these plaques are of different age (which indicates that the disease has been present for sometime now). Remember what I said –relapsing and remitting MS. Sometimes to help secure the diagnosis, your doctor shall also order a MRI scan of the spine most commonly cervical spine. The intention is the same and that is to see evidence of dissemination of the disease process in the brain and spinal cord.

Spinal tap: a lumbar puncture is usually carried out. Does every patient need a spinal tap to help secure the diagnosis of MS? No. Remember the diagnosis of MS can be made clinically in some patients. In patients where the characteristic history is not forthcoming and in whom the MRI scan does not prove helpful (does not evidence of dissemination of disease process in space and time), a spinal tap may be warranted.  The spinal fluid of MS patients is analyzed for certain proteins which suggest evidence of disease process. These include myelin basic protein (MBP), oligoclonal bands (OCBs) and IgG index.

Other tests: these tests may be requested in special circumstances (usually when the diagnosis remains elusive inspite of MRI scans and spinal tap).

1) Visual evoked potential (VEP), brainstem auditory evoked potential (BAEP) and somatosensory evoked potentials (SSEP):  these tests usually involve testing the integrity of different pathways in the brain. VEP tests the visual pathway from the eye to the occipital (visual) cortex, BAEP–tests the brainstem auditory pathways while SSEP check for the integrity of the white matter tracts carrying somatosensory information (vibration, joint sense and position sense) from the periphery (arm or leg) to the somatosensory cortex.  MS lesions involving any of these pathways cause a delay in the rate of conduction of nerve impulse and provide ancillary evidence of involvement of white matter tracts of the brain by a demyelinating disease process.

I hope these two posts help you all in understanding how the diagnosis of MS is made.

 

Nitin Sethi, MD

Brain disease weblog update and future directions

I apologize that I have not posted any new information on my blog for the past few months. Have no good excuse apart from the fact that work has kept me really busy. Thank you for all your questions. I have caught up with my answers and hopefully you shall find them informative.

It is time to get the blog up and running again. So I shall pick it up from where I left off and discuss MS in my next post.

 

Personal Regards,

Nitin Sethi, MD

Multiple Sclerosis–making the diagnosis

I still continue to get many questions from the readers of my blog regarding multiple sclerosis (MS). A significant majority of them write to me because they are concerned they may have MS either because of white matter lesions found on a MRI scan of the brain or because they are plagued by various non-specific signs and symptoms. Though I have written about this before, I thought this shall be a good time to go over how the diagnosis of MS is made. What are the symptoms that raise the suspicion for MS, what are the clinical signs on examination that suggest MS and finally what are the tests that may help to confirm the diagnosis.

Before I dwell deeper into this topic, please remember: THE DIAGNOSIS OF MS IS A CLINICAL ONE. Meaning that it can be made on the basis of a history and clinical examination itself. No tests are needed in such a situation to confirm the diagnosis.  Of course as it is often in medicine–it is always not that easy.

So let us begin—

Clinical history: Are there any points in the clinical history of the patient that suggest the diagnosis of MS? Patients with MS may give a history of neurological symptoms and signs (remember signs are elicted on clinical examination-meaning when the doctor examines you) that wax and wane (relapsing and remitting MS). A patient may present with acute loss of vision in one eye along with pain in the eye  (I am talking about optic neuritis). As the doctor dwells deeper into the history, the patient volunteers that a couple of years ago he had a similar problem in the other eye which had resolved on its own and he had not been investigated further. Hmmm–now we have history of 2 attacks separated in time. As a neurologist this makes me think of MS as a possible diagnosis. The problem with MS though is that it may present with non-specific signs or symptoms or rather it may present with signs and symptoms that localize to different parts of the central nervous system (CNS). By CNS I mean the brain and the spinal cord. So for example patients may present with numbness on weakness on one side of the body (this localizes to the contralateral motor or sensory cortex), problems with the bladder (incontinence–this usually localizes to the spinal cord), problems with balance and coordination (their gait is off and they may have a prominent tremor in their limbs–this localizes to the cerebellum or the brain stem), double vision (this localizes to the cranial nerves which control the movement of the eyes). Virtually any part of the central nervous system can be involved–hence the presentation is at times non-specific. BUT WHAT HELPS US AS DOCTORS IS WHEN WE GET HISTORY WHICH SUGGESTS A DISEASE DISSEMINATED IN SPACE AND IN TIME. Meaning a disease process which is involving different parts of the central nervous system and which has shown evidence of multiple attacks separated by time. REMEMBER MS IS NOT A MONOPHASIC ILLNESS (it relapses and remits!!!)

Clinical examination: So what are the clinical examination findings which make me as a neurologist think of MS in  a patient. There are certain neurological signs which have been said to be pathogonomic of MS (meaning the presence of these signs virtually seals the diagnosis of MS). These include certain eye signs. Bilateral internuclear opthalmoplegia (INO) (who said neurology was easy!!!) is one such sign. This is an eye-sign in which the patient’s eyes do not move as directed by the examiner. One eye fails to adduct (that is move inwards) while the other eye  abducts (moves outwards) but the abducting eye shows a nystagmus (shaky side to side movement). Other eye signs such as an afferent pupillary defect (this is elicted by shining a penlight into the eye) also raise suspicion for MS. What we as neurologists look for though is this–we look for signs that suggest the disease is disseminated in the CNS. REMEMBER WHAT I TOLD YOU ABOUT MS. IT IS A DISEASE WHICH IS DISSEMINATED IN TIME AND SPACE.

Tests: so when a diagnosis of MS cannot be made on the basis of history and examination alone, we as doctors have to fall back on tests to rule in or rule out the diagnosis. No test seals the diagnosis of MS by itself. They just help to add to our certainity. I shall discuss the various tests namely –imaging studies such as MRI scan of the brain and spinal cord., evoked potential studies such as visual evoked potential (VEP), somatosensory evoked potential (SSEP), brain stem auditory evoked potential (BAEP), spinal fluid (CSF) examination in the next post.

 

Nitin Sethi, MD